In addition to the human blood group systems, erythrocyte antigens exist which do not yet meet the definition of a blood group system. Most of these antigens are either nearly universal in human blood (high-prevalence antigens) or extremely rare (low-prevalence antigens). Reagents to test for these antigens are difficult to find and many cannot be purchased commercially to date.
The molecular genetic identity of many blood group antigens is well established and a variety of polymerase chain reaction (PCR)-based techniques exist for their detection. Many laboratories have developed in-house protocols or adopted the test systems of others for predicting blood group antigens by deoxyribonucleic acid (DNA) typing on a routine basis.
DNA-based assays can readily determine homozygosity and heterozygosity, and in some cases, hemizygosity of a blood group allele, which is beyond the capability of conventional serology. Another added benefit of DNA-based blood group typing beyond the capabilities of traditional serology is the possibility to determine the foetal blood group by testing DNA derived from foetal cells in amniotic fluid or chorionic villus biopsies, or increasingly common even from cell-free foetal DNA in maternal plasma.
It is a great frustration to end users and manufacturers alike that the limiting factor in providing phenotype information on patients, blood donors and reagent red blood cells (RBCs) is the availability of reliable antisera.
There are monoclonal antibodies to many blood group antigens and thus supply is somewhat assured. However, for specificities for which monoclonal antibodies have not been raised, manufacturers still have to rely on human polyclonal antibodies as typing reagents. Many of these are increasingly in short supply, are often only weakly and/or variablyreactive, and are costly to produce. For some blood groups, volunteers have been immunised against a certain blood group antigen for reagent or medical use but raising antibodies against a high-prevalence antigen, for instance Vel as described in Issit et al (1968) Vox Sang. 15: 125-132, is not an option in human volunteers because blood units lacking the corresponding antigen are rare and the procedure could therefore constitute a safety threat.
The Vel blood group antigen, first described by Sussman and Miller (Rev. Hematol. 1952; 7:368-71), is expressed in RBCs and is one of several so-called orphan blood group antigens for which the molecular basis is unknown.
Among the orphan blood groups, Vel is considered one of the most clinically relevant, as Vel negative patients, which have been immunised following transfusion or pregnancy, and subsequently transfused with red blood cells from Vel positive donors are at risk of severe side effects including acute intravascular hemolysis.
There is currently a global lack of Vel negative blood donors available for transfusion medicine purposes. Accordingly it is desirable to provide a test which fast and efficiently can select for Vel negative donors.
The molecular background of Vel has to date been unknown and thus the only possibility to identify blood donors lacking Vel has been through phenotyping using antisera from immunised patients, a suboptimal approach from an ethics, safety and quality perspective. Tools for genetic screening are desirable as they facilitate large-scale, cost-efficient screening of blood donors for the absence of Vel, in order to increase availability of Vel negative blood.
Identification of a gene on which Vel blood group expression is dependent would permit the possible development of a screening assay which could identify Vel negative blood donors, and also means to type patients at risk of producing an unwanted antibody against the Vel antigen, or suspected to have made such antibodies.